Search

We explored the frequency of CD14 - CD10 - CD45 + HLA-DR - SSC ++ neutrophils (CD10 - neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10 - neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10 - and CD10 + neutrophils were sorted, and their cytology was analyzed. CD3 + T cells were also isolated and cultured with the autologous CD10 - or CD10 + neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase-1 (Arg-1) and reactive oxygen species (ROS) in CD10 + or CD10 - neutrophils were examined. Few CD10 - neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10 - neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse-free survival and overall survival in patients with high CD10 - neutrophils were shorter than those with low CD10 - neutrophils. CD10 - neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T-cell proliferation and facilitate T-cell death. Furthermore, a significant increase was observed in Arg-1 expression, along with an increase to a certain extent in ROS. CD10 - neutrophils in patients with NHL have characteristics of myeloid-derived suppressor cells and may be related to disease progression and poor prognosis., (© 2024 Australian and New Zealand Society for Immunology, Inc.)

Background: Monocytic myeloid-derived suppressor cells (M-MDSCs) characterized with the phenotype of CD14 + HLA-DR low/- have attracted a lot of attention in the field of human tumor immunology. However, little is known about the roles of M-MDSCs in acute myeloid leukemia (AML) as opposed to their multiple roles in solid tumors., Methods: We examined the frequencies of M-MDSCs identified for CD14 + HLA-DR low/- by flow cytometry in the peripheral circulating blood of 109 newly diagnosed adult patients with AML and 30 healthy controls (HC). Then, we, respectively, validated the clinic significance of circulating M-MDSCs on the relevance of spectral features for diagnostic stratification, induction therapy response, treatment effect maintenance, and long-term survival in AML., Results: Circulating M-MDSC frequencies of AML were significantly higher than those of HC both in CD14 + monocytes (46.22% ± 2.95% vs. 1.07% ± 0.17%, p < 0.01) and peripheral blood mononuclear cells (PBMCs) (4.21% ± 0.80% vs. 0.17% ± 0.03%, p < 0.01). Elevated circulating M-MDSCs in patients with AML were significantly associated with low complete remission (CR) rate, high relapse/refractory rate, and poor long-term survival, but had no correlation with common clinic risks and cytogenetic molecular risk categories., Conclusions: It was demonstrated that circulating M-MDSCs are elevated and associated with poor prognosis in AML, suggesting M-MDSCs might be a prognostic indicator for AML., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Huiping Wang et al.)

In the past decade, much emphasis has been put on the transcriptional activation of HIV-1, which is proposed as a promised strategy for eradicating latent HIV-1 provirus. Two drugs, prostratin and hexamethylene bisacetamide (HMBA), have shown potent effects as inducers for releasing HIV-1 latency when used alone or in combination, although their cellular target(s) are currently not well understood, especially under drug combination. Here, we have shown that HMBA and prostratin synergistically release HIV-1 latency via different mechanisms. While prostratin strongly stimulates HMBA-induced HIV-1 transcription via improved P-TEFb activation, HMBA is capable of boosting NF-κB-dependent transcription initiation by suppressing prostratin-induced expression of the deubiquitinase A20, a negative feedback regulator in the NF-κB signaling pathway. In addition, HMBA was able to increase prostratin-induced phosphorylation and degradation of NF-κB inhibitor IκBα, thereby enhancing and prolonging prostratin-induced nuclear translocation of NF-κB, a prerequisite for stimulation of transcription initiation. Thus, by blocking the negative feedback circuit, HMBA functions as a signaling enhancer of the NF-κB signaling pathway.

Background . It is controversial whether lymphocyte infiltration exhibited in biopsy specimens is associated with transplant outcomes. This study focused on the effect of CD20-positive B cell infiltration in biopsy specimens from allografts with acute cellular rejection (ACR) in a Chinese population. Methods . Altogether, 216 patients transplanted from Sep. 2001 to Dec. 2014 with biopsy-proved ACR (Banff I or Banff II) were included in the analysis. Biopsies were immunostained for CD20 and C4d. Baseline information, serum creatinine and GFR before and after treatment, steroid resistance, response to treatment, graft loss, and survival were analyzed. Results . Eighty-three patients were classified into CD20-negative group, and 133 patients were classified into CD20-positive group. Significantly more CD20-negative patients (49/83, 59.0%) received steroid plus antibody therapy compared with the CD20-positive group (52/133, 39.1%) ( P = 0.004). The response to treatment for ACR did not differ between these two groups. The CD20-positive group had less graft loss (18.8% versus 32.5%, P = 0.022) and a better graft survival rate. Further exploration of the infiltration degree suggested that it tended to be positively related to graft survival, but this did not reach statistical significance. Conclusion . CD20-positive B cell infiltration in renal allograft biopsies with ACR is associated with less steroid resistance and better graft survival. The presence of CD20-positive B cells is protective for renal allografts., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

The present study was designed to investigate the effect of Agaricus brasiliensis extract (ABE) on phenylhydrazine-induced neonatal jaundice in rats. Administration of ABE dose-dependently reduced the elevated bilirubin level induced by phenylhydrazine. It can be somewhat supported from the results of in vitro bilirubin degradation experiment. ABE treatment also reduced the total antioxidant status (TAOS), cascade O2(-)/SOD, level of NF-κB protein, and adrenomedullin (AM). Overall, the results of this study demonstrated that Agaricus brasiliensis extract may be beneficial to reducing bilirubin level without causing hepatotoxicity in neonatal jaundice.

Prostratin has been proposed as a promising reagent for eradicating the latent HIV-1 provirus by inducing HIV-1 transcription activation. The molecular mechanism of this activation, however, is far from clear. Here, we show that the protein kinase D3 (PKD3) is essential for prostratin-induced transcription activation of latent HIV-1 provirus. First, silencing PKD3, but not the other members of PKD family, blocked prostratin-induced transcription of HIV-1. Second, overexpressing the constitutively active form of PKD3, but not the wild-type or kinase-dead form of PKD3, augmented the expression of HIV-1. Consistent with this observation, we found that prostratin could trigger PKD3 activation by inducing the phosphorylation of its activation loop. In addition, we identified PKCε of the novel PKC subfamily as the upstream kinase for this phosphorylation. Finally, the activation effect of PKD3 on HIV-1 transcription was shown to depend on the presence of κB element and the prostratin-induced activation of NF-κB, as indicated by the fact that silencing PKD3 blocked prostratin-induced NF-κB activation and NF-κB-dependent HIV-1 transcription. Therefore, for the first time, PKD3 is implicated in the transcription activation of latent HIV-1 provirus, and our results revealed a molecular mechanism of prostratin-induced HIV-1 transcription via PKCε/PKD3/NF-κB signaling pathway.